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Abstract There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Abstract Social memory impairment is a key symptom of many brain disorders, but its underlying mechanisms remain unclear. Neuroligins (NLGs) are a family of cell adhesion molecules essential for synapse development and function and their dysfunctions are linked to neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. Although NLGs are extensively studied in neurons, their role in glial cells is poorly understood. Here we show that astrocytic deletion of NLG3 in the ventral hippocampus of adult male mice impairs social memory, attenuates astrocytic Ca2+ signals, enhances the expression of EAAT2 and prevents long-term potentiation, and these impairments are rescued by increasing astrocyte activity, reducing EAAT2 function or enhancing adenosine/A2a receptor signaling. This study has revealed an important role of NLG3 in astrocyte function, glutamate homeostasis and social memory and identified the glutamate transporter and adenosine signaling pathway as potential therapeutic strategies to treat brain disorders.

Abstract Boron-doped biochar (B-BC) was synthesized by pyrolysis using solid waste of sorghum straw as raw material. The specific surface area of B-BC increased significantly by 2.38 times compared to that of pure BC. This enhancement allowed B-BC (0.3 g L−1) to achieve complete adsorption of 10 mg L−1 tartrazine (TTZ) within 40 min. Moreover, acidic conditions were more favorable for TTZ adsorption, achieving complete removal of TTZ in only 15 min at a pH of 3.0. Interestingly, the adsorption rate of TTZ by B-BC in the presence of 0.05 M Cl− was approximately 2.12 times higher than that in the absence of Cl−. When other background electrolytes were present, excluding PO4 3−, complete adsorption of TTZ could also be achieved within 60 min. Thermodynamic analysis and DFT calculations described the parameters of B-BC for TTZ adsorption, including $$\Delta {\text{G}}^{\Theta }$$ Δ G Θ (

Abstract Background: Both lipid metabolism and obesity are crucial factors in osteoporosis, influencing the relevance of the cardiometabolic index (CMI), a new body fat index incorporating obesity and lipid metrics. Our study aims to explore the relationship between CMI and lumbar spine bone mineral density (BMD) and the mediating role of body fat percentage. Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2018, we conducted a cross-sectional analysis. We employed multiple linear regression models, subgroup analyses, generalized additive models (GAM), smooth curve fitting, and mediation analysis to evaluate the linear and nonlinear relationships between CMI and lumbar spine BMD. Results: The study involved 5,124 participants with an average lumbar spine BMD of 1.03 ± 0.15 g/cm2. We identified a negative correlation between CMI and lumbar spine BMD (β = -0.015; 95% CI: -0.023, -0.008). Nonlinear associations were evident, with inflection points at CMI values of 1.12 and 2.86. Subgroup analyses showed consistent negative correlations across all categories without significant differences (p for interaction > 0.05). Moreover, body fat percentage negatively correlated with BMD (β = -0.005; 95% CI: -0.006, -0.004) and mediated 9.41% of the relationship between CMI and BMD. Conclusion: Increased CMI levels are associated with lower lumbar spine BMD, with body fat percentage significantly mediating this relationship. This underscores the importance of managing body composition in the context of bone health, highlighting CMI’s potential utility in osteoporosis risk assessment.

Abstract RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism, but a comprehensive picture of RBP expression across tissues is lacking. Here, we describe our development of the method we call HARD-AP that robustly retrieves RBPs and tightly associated RNA regulatory complexes from cultured cells and fresh tissues. We successfully use HARD-AP to establish a comprehensive atlas of RBPs across mouse primary organs. We then systematically map RNA-binding sites of these RBPs using machine learning-based modeling. Notably, the modeling reveals that the LIM domain as an RNA-binding domain in many RBPs. We validate the LIM-domain-only protein Csrp1 as a tissue-dependent RNA binding protein. Taken together, HARD-AP is a powerful approach that can be used to identify RBPomes from any type of sample, allowing comprehensive and physiologically relevant networks of RNA-protein interactions.

Abstract Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P

Abstract Background Premature ovarian insufficiency (POI) is a condition characterized by a substantial decline or loss of ovarian function in women before the age of 40. However, the pathogenesis of POI remains to be further elucidated, and specific targeted drugs which could delay or reverse ovarian reserve decline are urgently needed. Abnormal DNA damage repair (DDR) and cell senescence in granulosa cells are pathogenic mechanisms of POI. Ubiquitin-specific protease 14 (USP14) is a key enzyme that regulates the deubiquitylation of DDR-related proteins, but whether USP14 participates in the pathogenesis of POI remains unclear. Methods We measured USP14 mRNA expression in granulosa cells from biochemical POI (bPOI) patients. In KGN cells, we used IU1 and siRNA-USP14 to specifically inhibit USP14 and constructed a cell line stably overexpressing USP14 to examine its effects on DDR function and cellular senescence in granulosa cells. Next, we explored the therapeutic potential of IU1 in POI mouse models induced by D-galactose. Results USP14 expression in the granulosa cells of bPOI patients was significantly upregulated. In KGN cells, IU1 treatment and siUSP14 transfection decreased etoposide-induced DNA damage levels, promoted DDR function, and inhibited cell senescence. USP14 overexpression increased DNA damage, impaired DDR function, and promoted cell senescence. Moreover, IU1 treatment and siUSP14 transfection increased nonhomologous end joining (NHEJ), upregulated RNF168, Ku70, and DDB1, and increased ubiquitinated DDB1 levels in KGN cells. Conversely, USP14 overexpression had the opposite effects. Intraperitoneal IU1 injection alleviated etoposide-induced DNA damage in granulosa cells, ameliorated the D-galactose-induced POI phenotype, promoted DDR, and inhibited cell senescence in ovarian granulosa cells in vivo. Conclusions Upregulated USP14 in ovarian granulosa cells may play a role in POI pathogenesis, and targeting USP14 may be a potential POI treatment strategy. Our study provides new insights into the pathogenesis of POI and a novel POI treatment strategy.

Lung cancer, highly prevalent and the leading cause of cancer-related death globally, persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic interventions. Recently, extracellular vesicles (EVs), functioning as natural carriers for intercellular communication, have received increasing attention due to their ability to traverse biological barriers and deliver diverse biological cargoes, including cytosolic proteins, cell surface proteins, microRNA, lncRNA, circRNA, DNA, and lipids. EVs are increasingly recognized as a valuable resource for non-invasive liquid biopsy, as well as drug delivery platforms, and anticancer vaccines for precision medicine in lung cancer. Herein, given the diagnostic and therapeutic potential of tumor-associated EVs for lung cancer, we discuss this topic from a translational standpoint. We delve into the specific roles that EVs play in lung cancer carcinogenesis and offer a particular perspective on how advanced engineering technologies can overcome the current challenges and expedite and/or enhance the translation of EVs from laboratory research to clinical settings.

Abstract Background Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021–2022. Methods A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. Results The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). Conclusion In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.

Abstract Recently, multi-modal vision-language foundation models have gained significant attention in the medical field. While these models offer great opportunities, they still face crucial challenges, such as the requirement for fine-grained knowledge understanding in computer-aided diagnosis and the capability of utilizing very limited or even no task-specific labeled data in real-world clinical applications. In this study, we present MaCo, a masked contrastive chest X-ray foundation model that tackles these challenges. MaCo explores masked contrastive learning to simultaneously achieve fine-grained image understanding and zero-shot learning for a variety of medical imaging tasks. It designs a correlation weighting mechanism to adjust the correlation between masked chest X-ray image patches and their corresponding reports, thereby enhancing the model’s representation learning capabilities. To evaluate the performance of MaCo, we conducted extensive experiments using 6 well-known open-source X-ray datasets. The experimental results demonstrate the superiority of MaCo over 10 state-of-the-art approaches across tasks such as classification, segmentation, detection, and phrase grounding. These findings highlight the significant potential of MaCo in advancing a wide range of medical image analysis tasks.

In this study, a crack-free pyrolysis process of partially cured precursor powder compacts was developed to prepare dense silicon boron carbonitride (SiBCN) monoliths at much lower temperatures (1300 °C), thereby circumventing the challenges of sintering densification (> 1800 °C). Unlike the elastic fracture in over-cured precursors or the viscoelastic deformation in under-cured precursors, the partially cured precursor, exhibiting elastic‒plastic deformation behavior, facilitates limited nanoscale pore formation in a dense structure, achieving a balance between crack-free pyrolysis and densification. Compared to SiBCN derived from the over-cured precursor (σ = ~159 MPa, KIC = 1.9 MPa·m1/2, Vickers hardness (HV) = 7.8 GPa, and E = 122 GPa), the resulting SiBCN monolith exhibited significantly improved mechanical properties (σ = ~304 MPa, KIC = 3.7 MPa·m1/2, HV = 10.6 GPa, and E = 161 GPa) and oxidation resistance. In addition, this study investigated the high-temperature performance of SiBCN monoliths, including crystallization and oxidation, and determined the oxidation kinetics induced by pore structure healing and the different oxidation mechanisms of Si–C–N and B–C–N clusters in the amorphous structure. Due to its unique composition and structure, the SiBCN ceramic oxide layer exhibits exceptional self-healing effects on repairing the nanoporous system in the initial stage and shows outstanding high-temperature stability during prolonged oxidation, mitigating adverse effects from bubble formation and crystallization. Due to the nanoporous structure, the oxidation rate is initially controlled by gas diffusion following a linear law before transitioning to oxide layer diffusion characterized by a parabolic law. Finally, due to different valence bond configurations, Si–C–N transforms into an amorphous SiCNO structure after phase separation, unlike the nucleation and growth of residual B–N–C.

Abstract Background Academic pressure and frustration stimulation are significant stressors in college students, and response to the prolonged stimuli would cause adverse mental and physical outcomes. However, more is needed to know about the stress response and its predictors among undergraduate nursing students retaking failed course under the background of the abolition of the Final Supplementary Examination in China. This study aimed to investigate the stress response and its predictive factors of nursing student repeaters who are retaking at least one failed course. Methods A cross-sectional study was conducted, utilizing convenience sampling to recruit 120 nursing student repeaters from four 4-year undergraduate medical universities in China between September 2020 and May 2021. Data collection instruments included a general information questionnaire, a stress response questionnaire, the Connor-Davidson resilience scale, a self-control scale, and a academic self-efficacy questionnaire. The data were analyzed using descriptive statistics, Pearson correlation coefficients, t-tests, analysis of variance (ANOVA), and multiple linear regression. Results The average scores of the total stress response, emotional response, physical response, and behavioral response were 58.07 ± 26.72, 86.97 ± 17.12, 57.69 ± 9.75, 67.16 ± 9.22, respectively. Stress response was predicted by psychological resilience, self-control ability, academic self-efficacy and the number of retaking courses. Conclusions The stress response among nursing student repeaters is relatively active. Higher psychological resilience, self-control ability, and academic self-efficacy predict lower levels of stress response. In order to help nursing students with failing and repeating course release their psychological stress and maintain well-being, nursing educators could adopt self-control promotion strategies and emphasize the cultivation of psychological resilience and academic self-efficacy as parts of health promotion programs for this particular student group.

Abstract Background Left Bundle Branch Area Pacing (LBBaP) is a cardiac pacing technique designed to mimic the natural conduction system of the heart. Traditional right ventricular apical pacing has been associated with increased risks of heart failure and atrial fibrillation. This study investigates the stability and safety of LBBaP using the Selectra 3D sheath (Biotronik) with an inclined angle for implanting the Solia S lead (Biotronik, SE & Co, KG). Methods A single-center retrospective study was conducted on 25 patients who underwent LBBaP implantation using the Selectra 3D sheath at our hospital. The procedure involved inserting the Solia S lead into the interventricular septum at an inclined angle. Surgical and postoperative data were collected, including the success rate, depth and angle of electrode insertion, complications, and follow-up data. Results The success rate of LBBaP implantation was 92%. The length of electrode insertion into the interventricular septum ranged from 12 to 23.0 mm, with an average of 18.1 ± 3.08 mm. The angle formed between the electrode and the septum ranged from 0° to 57.3°, with an average of 35.14°±14.31°. During the 3-month follow-up period, pacing parameters remained stable, and no complications were reported. Conclusions LBBaP implantation using the Selectra 3D sheath with an inclined angle for the Solia S implantation demonstrates stability and safety. The procedure boasts a high success rate and offers an effective option for LBBaP implantation.

Abstract Background R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. Results In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. Conclusion This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.

Abstract Sorghum ratooning, a time and labor-saving cultivation practice, is increasingly being adopted by farmers in Southwest China as an alternative. Efficient N fertilizer management is critical for economical production of sorghum and the long-term protection of the environment. To investigate the impact of N management on grain yield and nitrogen use efficiencies (NUEs) of ratoon sorghum system, a three-year field experiment was conducted for Jinyunuo3 (a hybrid cultivar) and Guojiaohong1 (an inbred cultivar) using 12 combinations of N rates and splitting ratios. The results showed that increasing N rate and splitting application times led to improvements in various growth parameters such as dry matter weight, crop growth rate (CGR), leaf area index (LAI), and photosynthetic potential (PP). The main, ratoon, and annual yields increased with N rate increase, but there was no significant difference between 225 and 150 kg N ha−1 in the ratoon and annual yields. Splitting the application of N fertilizer enhanced grain yield compared to a single dose application method, especially three-split applications yielded higher than two-split applications. Compared with N rates of 225 and 150 kg ha−1, N rate of 75 kg ha−1 increased apparent recovery rate of applied nitrogen (REN), agronomic efficiency of applied nitrogen (AEN), and partial factor productivity from applied nitrogen (PFPN) in both main season and whole year. But through splitting application methods at high N rates could achieve similar or even higher levels of NUEs compared to all applied as basal fertilizer at low N rates. Therefore, it could be recommended that applying 150 kg N ha−1 with a basal-jointing-heading fertilizer ratio of 2:4:4 represented an efficient N management practice to synchronously obtain high grain yield and NUEs in ratoon sorghum system in Southwest China.

Abstract RNA interference (RNAi) is a powerful tool for sequence-specific gene knockdown in therapeutic and research applications. However, spatiotemporal control of RNAi is required to decrease nonspecific targeting, potential toxicity, and allow targeting of essential genes. Herein we describe a class of de-novo-designed RNA switches that enable sequence-specific regulation of RNAi in mammalian cells. Using cis-repressing RNA elements, we engineer RNA devices that only initiate microRNA biogenesis when binding with cognate trigger RNAs. We demonstrate that this conditional RNAi system, termed Orthogonal RNA Interference induced by Trigger RNA (ORIENTR), provides up to 14-fold increases in artificial miRNA biogenesis upon activation in orthogonal libraries. We show that integration of ORIENTR triggers with dCas13d enhances dynamic range to up to 31-fold. We further demonstrate that ORIENTR can be applied to detect endogenous RNA signals and to conditionally knockdown endogenous genes, thus enabling regulatory possibilities including cell-type-specific RNAi and rewiring of transcriptional networks via RNA profile.

This paper investigated the association between students' perceptions of teacher autonomy-supportive and controlling interpersonal behaviours, positive and negative academic emotions, and subjective vitality and emotional exhaustion. Study 1 employed a cross-sectional survey design to collect data from 328 undergraduate students from three public universities in China. Study 2 employed an experimental design and collected data from 64 undergraduate students. The results of the structural equation modelling with latent variables indicated that teacher autonomy-supportive interpersonal behaviours did not reduce negative academic emotions, and negative emotions did not explain subjective vitality, while positive emotions did not explain emotional exhaustion. These findings suggest that positive and negative emotions are mutually exclusive in predicting subjective vitality and emotional exhaustion. The study discusses the implications of these findings for instructors' interpersonal behaviours and the role of emotions in predicting students' psychological well-being in the Chinese context.

"Research Findings:" This study aimed to examine the effectiveness of the Puhui early education services (PEES) policy in China from the triangulated perspectives of stakeholders using a developed and validated scale. First, applying a stratified cluster sampling method, the Puhui Early Education Services Policy Effectiveness Scale (PE) was developed and validated with 85 principals, 909 kindergarten teachers, and 4,128 parents. Second, the psychometric properties indicated that the PE was a reliable and valid scale with three constructs: accessibility, affordability, and quality. Third, descriptive statistics found that Chinese stakeholders submitted a positive evaluation of the PEES policy effectiveness, with the construct of quality ranked the highest and that of affordability the lowest. Fourth, parents have fewer positive evaluations compared to principals and teachers, while stakeholders from Puhui private kindergartens have more positive evaluations compared to those from public kindergartens. Last, hierarchical regression analysis found that kindergarten type and rating were critical positive predictors after controlling for demographic and urbanicity factors. "Practice or Policy:" These findings indicate that it is necessary to understand parents' policy expectations and improve the financial distribution to ensure sustainable and high-quality development of the PEES.

Research Findings: The current study explored the average levels, latent profiles, and predictors of preschoolers' cultural cognition, in a sample of 8774 preschoolers' parents in Shanghai, China. Parents with children aged 3-6 years completed measures of "Cultural Cognition Scale for Preschoolers" (CCSP) which was newly developed and validated. First, the psychometric properties indicated that CCSP was a reliable and valid scale with four constructs: cultural knowledge, cultural interest, cultural identity, and cultural practice. Second, preschoolers negatively performed in cultural cognition with few high-quality cultural practices and limited fundamental cultural knowledge. Third, the latent profile analysis yielded low-(28.0%), middle-(53.8%), and high-level (18.2%) profiles of parent reports, differentiated by parental education, child age, child gender, preschool rating, and location. Last but not least, a hierarchical regression analysis predicting preschoolers' cultural cognition found that child age, child gender, and parental education had critical effects. In addition, interaction effects were found between parental education and child age on cultural knowledge, as well as between child age and gender on cultural practice. Practice or Policy: This study provides a useful tool to understand and evaluate preschoolers' cultural cognition ability. The findings imply that excellent national cultural enlightenment education with more high-quality cultural activities for preschoolers needs additional focus. Besides, the characteristics of the children with the identified profiles and the family factors related to cultural cognition serve as a reference to better advance children's humanistic literacy.

ABSTRACTBackground Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001.Research design and methods This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured.Results No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group.Conclusions Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted.Trial Registration This trial was registered with ClinicalTrials.gov (NCT05552573).